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New test predicts the risk of non-hereditary breast cancer

27 June 2014

A simple blood test is currently in development that could help predict the likelihood of a woman developing breast cancer, even in the absence of a high-risk BRCA1 gene mutation, according to new UCL research.

The research, published in Genome Medicine, identifies an epigenetic
signature in the blood of women predisposed for breast cancer owing to an
inherited genetic mutation of the BRCA1
gene. Epigenetic alterations are thought to be key molecular switches that are
involved in the development of cancer. Strikingly, the same signature was
discovered in the blood of women without a BRCA1
mutation but who went on to develop breast cancer, making it a potential early
marker of women’s cancer in the general population.

BRCA1 mutation is inherited from a parent, and is the cause of at least
ten percent of breast cancers. The cause of the remaining 90% of sporadic
breast cancers in non-mutation carriers remains to be explained. Scientists are
beginning to understand that genetic mutations are not the sole contributors to
disease development and that the way in which genes are arranged in our cells
can affect whether they function appropriately – that is, whether they are
turned on or off. The arrangement and expression of our genes is overseen by
the process of epigenetics. One of the most studied epigenetic mechanisms is a
process called DNA methylation, which was the focus of the current study.

It shows the potential of a blood based epigenetic test to identify breast cancer risk in women without known predisposing genetic mutations

Professor Martin Widschwendter

In this study, researchers used blood samples collected several years
before breast cancer development from two large UK cohorts of women – the MRC
National Survey of Health and Development and the UK Collaborative Trial of
Ovarian Cancer Screening. They looked at the DNA methylation signature from
blood of those women with and without BRCA1
mutations. When this signature was applied to samples from both these groups,
those women who developed non-hereditary cancers were found to have the same DNA
methylation signature.

Professor Martin Widschwendter, the study’s lead author and head of the
UCL Department of Women’s Cancer, says: “We identified an epigenetic signature
in women with a mutated BRCA1 gene
that was linked to increased cancer risk and lower survival rates. Surprisingly,
we found the same signature in large cohorts of women without the BRCA1 mutation and it was able to
predict breast cancer risk several years before diagnosis.”

The researchers believe the epigenetic signature they found is
consistent with the idea that changes in the epigenome of immune cells are key
to cancer progression. The signature may be responsible for silencing genes in
immune cells, which in turn could affect the ability of the immune system to
prevent breast cancer development. Further research needs to be done to find
out whether this epigenetic signature is just an indicator of breast cancer
risk or is involved with the progression of breast cancer. Work is now
proceeding on using these findings in the clinical setting.

Professor Widschwendter says: “The data is encouraging since it
shows the potential of a blood based epigenetic test to identify breast cancer
risk in women without known predisposing genetic mutations.”

The work was
jointly funded by The Eve Appeal and the National Institute for Health Research
(NIHR) University College London Hospitals Biomedical Research Centre.

A key component in
the successful development of Prof Widschwendter’s Department of Women’s Cancer
at UCL has been their relationship with The Eve Appeal. The charity has grown
and developed in parallel with the Department and has played a crucial role in
providing seed funding, core infrastructure funding and project funding in
addition to campaigning to raise awareness of women-specific cancers. Much work
remains to be done and the kind of support provided by The Eve Appeal is vital.